Designing stem cell niches for differentiation and self-renewal

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries

The typical developmental trajectory of social and executive functions in late adolescence and early adulthood.

Executive functions and social cognition develop through childhood into adolescence/early adulthood and are important for adaptive goal-oriented behaviour (Apperly, Samson & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood (Barker, Andrade, Morton, Romanowski & Bowles, 2010; Lebel, Walker, Leemans, Phillips & Beaulieu, 2008) although social cognition functions are also associated with widely distributed networks. Previously, non-linear development has been reported around puberty on an emotion match to sample task (McGivern, Andersen, Byrd, Mutter & Reilly, 2002) and for IQ in mid adolescence (Ramsden et al., 2011). However, there are currently little data on the typical development of social and executive functions in late adolescence and early adulthood. In a cross sectional design, 98 participants completed tests of social cognition and executive function, Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999), Positive and Negative Affect Scale (Watson, Clark & Tellegan, 1988), Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983) and measures of pubertal development and demographics at age 17, 18 and 19. Non-linear age differences for letter fluency and concept formation executive functions were found, with a trough in functional ability in 18 year olds compared to other groups. There were no age group differences on social cognition measures. Gender accounted for differences on one scale of concept formation, one dynamic social interaction scale and two empathy scales. The clinical, developmental and educational implications of these findings are discussed

From cognitive science to cognitive neuroscience to neuroeconomics

As an emerging discipline, neuroeconomics faces considerable methodological and practical challenges. In this paper, I suggest that these challenges can be understood by exploring the similarities and dissimilarities between the emergence of neuroeconomics and the emergence of cognitive and computational neuroscience two decades ago. From these parallels, I suggest the major challenge facing theory formation in the neural and behavioural sciences is that of being under-constrained by data, making a detailed understanding of physical implementation necessary for theory construction in neuroeconomics. Rather than following a top-down strategy, neuroeconomists should be pragmatic in the use of available data from animal models, information regarding neural pathways and projections, computational models of neural function, functional imaging and behavioural data. By providing convergent evidence across multiple levels of organization, neuroeconomics will have its most promising prospects of success

Bestial boredom: a biological perspective on animal boredom and suggestions for its scientific investigation

Boredom is likely to have adaptive value in motivating exploration and learning, and many animals may possess the basic neurological mechanisms to support it. Chronic inescapable boredom can be extremely aversive, and understimulation can harm neural, cognitive and behavioural flexibility. Wild and domesticated animals are at particular risk in captivity, which is often spatially and temporally monotonous. Yet biological research into boredom has barely begun, despite having important implications for animal welfare, the evolution of motivation and cognition, and for human dysfunction at individual and societal levels. Here I aim to facilitate hypotheses about how monotony affects behaviour and physiology, so that boredom can be objectively studied by ethologists and other scientists. I cover valence (pleasantness) and arousal (wakefulness) qualities of boredom, because both can be measured, and I suggest boredom includes suboptimal arousal and aversion to monotony. Because the suboptimal arousal during boredom is aversive, individuals will resist low arousal. Thus, behavioural indicators of boredom will, seemingly paradoxically, include signs of increasing drowsiness, alongside bouts of restlessness, avoidance and sensation-seeking behaviour. Valence and arousal are not, however, sufficient to fully describe boredom. For example, human boredom is further characterized by a perception that time ‘drags’, and this effect of monotony on time perception can too be behaviourally assayed in animals. Sleep disruption and some abnormal behaviour may also be caused by boredom. Ethological research into this emotional phenomenon will deepen understanding of its causes, development, function and evolution, and will enable evidence-based interventions to mitigate human and animal boredom

Examining affective-motivational dynamics and behavioral implications within the interpersonal context of pain

Emotional, motivational, and interpersonal dimensions are considered integral to pain experience but have largely been examined separately. In this focus article, we argue that an integrative theoretical account that acknowledges each of these elements is a critical next step to capture the complexity and nuance of interpersonal pain dynamics and to shape future research. The aim of this focus article is to provide a foundation for such an account by drawing upon established insights from appraisal theory of emotion, influential behavioral models, empathy/interpersonal pain research, and social psychology literature to highlight conceptual relationships, potential mechanisms of action, and avenues of inquiry that have not previously been examined in the context of pain. Specifically, we highlight the interpersonal nature of pain and the conceptual relationship between emotion and motivation in pain experience. We discuss an affective-motivational tension between self- and other-oriented goals that can arise within the interpersonal pain context, and how such dynamics may affect the nature and effectiveness of care giving behavior. We then describe the role of emotion regulation and strategies that may facilitate optimal interpersonal pain dynamics and caregiving within a multiple goal context. Finally, we outline a foundation for an integrative theoretical model and directions for future research. Perspective: Drawing upon insights from appraisal theory of emotion, empathy/interpersonal pain research, influential behavioral models, and social psychology literature, this focus article provides a foundation for an integrative affective-motivational account of interpersonal pain dynamics as a basis for theoretical and clinical advancement. (C) 2017 by the American Pain Societ

Dwelling Quietly in the Rich Club: Brain Network Determinants of Slow Cortical Fluctuations

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously -- elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala, and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow time scales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding "feeder" cortical regions show unstable, rapidly fluctuating dynamics likely crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics.Comment: 35 pages, 6 figure

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages

Toward bio-inspired information processing with networks of nano-scale switching elements

Unconventional computing explores multi-scale platforms connecting molecular-scale devices into networks for the development of scalable neuromorphic architectures, often based on new materials and components with new functionalities. We review some work investigating the functionalities of locally connected networks of different types of switching elements as computational substrates. In particular, we discuss reservoir computing with networks of nonlinear nanoscale components. In usual neuromorphic paradigms, the network synaptic weights are adjusted as a result of a training/learning process. In reservoir computing, the non-linear network acts as a dynamical system mixing and spreading the input signals over a large state space, and only a readout layer is trained. We illustrate the most important concepts with a few examples, featuring memristor networks with time-dependent and history dependent resistances

The effects of dividing attention on smooth pursuit eye tracking

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